Carboxylic tris-like siloxanyl monomers

ABSTRACT

The present invention relates to polymeric compositions useful in the manufacture of biocompatible medical devices. More particularly, the present invention relates to certain carboxylic monomers capable of polymerization to form polymeric compositions having desirable physical characteristics useful in the manufacture of ophthalmic devices. The polymeric compositions comprise polymerized carboxylic hydrophilic siloxanyl monomers.

PRIORITY CLAIMS TO PRIOR APPLICATIONS

None

CROSS-REFERENCE TO RELATED APPLICATIONS

None

FIELD

The present invention relates to polymeric compositions useful in themanufacture of biocompatible medical devices. More particularly, thepresent invention relates to certain carboxylic siloxanyl monomerscapable of polymerization to form polymeric compositions havingdesirable physical characteristics useful in the manufacture ofophthalmic devices.

BACKGROUND AND SUMMARY

Various articles, including biomedical devices, are formed oforganosilicon-containing materials. One class of organosilicon materialsuseful for biomedical devices, such as soft contact lenses, issilicon-containing hydrogel materials. A hydrogel is a hydrated,crosslinked polymeric system that contains water in an equilibriumstate. Hydrogel contact lenses offer relatively high oxygen permeabilityas well as desirable biocompatibility and comfort. The inclusion of asilicon-containing material in the hydrogel formulation generallyprovides higher oxygen permeability since silicon based materials havehigher oxygen permeability than water.

Another class of organosilicon materials is rigid, gas permeablematerials used for hard contact lenses. Such materials are generallyformed of silicon or fluorosilicon copolymers. These materials areoxygen permeable, and more rigid than the materials used for softcontact lenses. Organosilicon-containing materials useful for biomedicaldevices, including contact lenses, are disclosed in the following U.S.patents: U.S. Pat. No. 4,686,267 (Ellis et al.); U.S. Pat. No. 5,034,461(Lai et al.); and U.S. Pat. No. 5,070,215 (Bambury et al.).

Silicon-containing materials are of keen interest as ophthalmicmaterials as they have characteristically high gas permeability, butsuffer the disadvantage of being very hydrophobic. This hydrophobicityresults in poor wettability and comfort of the resulting materials whenin contact with the cornea, and creates difficulty in compatibilizingsuch silicon-containing monomers with hydrophilic monomers to result ina transparent copolymer with an ideal blend of properties.

Soft contact lens materials are made by polymerizing and crosslinkinghydrophilic monomers such as 2-hydroxyethyl methyacrylate,N-vinyl-2-pyrrolidone, methacrylic acid and combinations thereof. Thepolymers produced by polymerizing these hydrophilic monomers exhibitsignificant hydrophilic character themselves and are capable ofabsorbing a significant amount of water in their polymeric matrices. Dueto their ability to absorb water, these polymers are often referred toas “hydrogels”. These hydrogels are optically clear and, due to theirhigh levels of water of hydration, are particularly useful materials formaking soft contact lenses. Siloxane-type monomers are well known to bepoorly soluble in water as well as hydrophilic solvents and monomers andare therefore difficult to copolymerize and process using standardhydrogel techniques. Therefore, there is a need for new siloxane-typemonomers that have improved solubility in the materials, specificallythe diluents, used to make hydrogel lenses. Further, there is a need formonomers that result in a polymerized medical device that is extractablein water instead of the organic solvents used in the prior art.

The present invention provides novel carboxylic organosilicon-containingmonomers which are useful in articles such as biomedical devicesincluding contact lenses.

BRIEF DESCRIPTION OF THE DRAWINGS

None

DETAILED DESCRIPTION

In a first aspect, the invention relates to monomers of formula (I):

wherein L, when present, can be the same or different and is selectedfrom the divalent group consisting of a bond, a straight or branchedC1-C30 alkyl group, a C1-C30 fluoroalkyl group, a C1-C20ester-containing group, an alkyl ether, cycloalkyl ether cycloalkenylether, aryl ether, arylalkyl ether, a polyether containing group, asubstituted or unsubstituted C3-C30 cycloalkyl group, a substituted orunsubstituted C3-C30 cycloalkylalkyl group, a substituted orunsubstituted C3-C30 cycloalkenyl group, a substituted or unsubstitutedC5-C30 aryl group, a substituted or unsubstituted C5-C30 arylalkylgroup, a substituted or unsubstituted C5-C30 heteroaryl group, asubstituted or unsubstituted C3-C30 heterocyclic ring, a substituted orunsubstituted C4-C30 heterocyclolalkyl group, a substituted orunsubstituted C6-C30 heteroarylalkyl group, a C5-C30 fluoroaryl group,or a hydroxyl substituted alkyl ether and combinations thereof; X is H,one equivalent alkali metal, or ½ equivalent alkaline earth metal; R isindependently hydrogen, a straight or branched C1-C30 alkyl group, aC1-C30 fluoroalkyl group, a C1-C20 ester-containing group, an alkylether, cycloalkyl ether, cycloalkenyl ether, aryl ether, arylalkylether, a polyether containing group, a substituted or unsubstitutedC1-C30 alkoxy group, a substituted or unsubstituted C3-C30 cycloalkylgroup, a substituted or unsubstituted C3-C30 cycloalkylalkyl group, asubstituted or unsubstituted C3-C30 cycloalkenyl group, a substituted orunsubstituted C5-C30 aryl group, a substituted or unsubstituted C5-C30arylalkyl group, a substituted or unsubstituted C5-C30 heteroaryl group,a substituted or unsubstituted C3-C30 heterocyclic ring, a substitutedor unsubstituted C4-C30 heterocyclolalkyl group, a substituted orunsubstituted C6-C30 heteroarylalkyl group, fluorine, a C5-C30fluoroaryl group, or a hydroxyl group; and V is independently apolymerizable ethylenically unsaturated organic radical. It should berealized that the polymerizable ethylenically unsaturated organicradical may be internal or external to the L groups as shown in thefigures below.

Representative examples of urethanes for use herein include, by way ofexample, a secondary amine linked to a carboxyl group which may also belinked to a further group such as an alkyl. Likewise the secondary aminemay also be linked to a further group such as an alkyl.

Representative examples of carbonates for use herein include, by way ofexample, alkyl carbonates, aryl carbonates, and the like.

Representative examples of carbamates, for use herein include, by way ofexample, alkyl carbamates, aryl carbamates, and the like.

Representative examples of carboxyl ureidos, for use herein include, byway of example, alkyl carboxyl ureidos, aryl carboxyl ureidos, and thelike.

Representative examples of sulfonyls for use herein include, by way ofexample, alkyl sulfonyls, aryl sulfonyls, and the like.

Representative examples of alkyl groups for use herein include, by wayof example, a straight or branched hydrocarbon chain radical containingcarbon and hydrogen atoms of from 1 to about 18 carbon atoms with orwithout unsaturation, to the rest of the molecule, e.g., methyl, ethyl,n-propyl, 1-methylethyl (isopropyl), n-butyl, n-pentyl, etc., and thelike.

Representative examples of fluoroalkyl groups for use herein include, byway of example, a straight or branched alkyl group as defined abovehaving one or more fluorine atoms attached to the carbon atom, e.g.,—CF3, —CF2CF3, —CH2CF3, —CH2CF2H, —CF2H and the like.

Representative examples of ester-containing groups for use hereininclude, by way of example, a carboxylic acid ester having one to 20carbon atoms and the like.

Representative examples of ether or polyether containing groups for useherein include, by way of example, an alkyl ether, cycloalkyl ether,cycloalkylalkyl ether, cycloalkenyl ether, aryl ether, arylalkyl etherwherein the alkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, aryl, andarylalkyl groups are defined above, e.g., alkylene oxides, poly(alkyleneoxide)s such as ethylene oxide, propylene oxide, butylene oxide,poly(ethylene oxide)s, poly(ethylene glycol)s, poly(propylene oxide)s,poly(butylene oxide)s and mixtures or copolymers thereof, an ether orpolyether group of the general formula —R8OR9, wherein R8 is a bond, analkyl, cycloalkyl or aryl group as defined above and R9 is an alkyl,cycloalkyl or aryl group as defined above, e.g., —CH2CH2OC6H5 and—CH2CH2OC2H5, and the like.

Representative examples of amide groups for use herein include, by wayof example, an amide of the general formula —R10C(O)NR11R12 wherein R10,R11 and R12 are independently C1-C30 hydrocarbons, e.g., R10 can bealkylene groups, arylene groups, cycloalkylene groups and R11 and R12can be alkyl groups, aryl groups, and cycloalkyl groups as definedherein and the like.

Representative examples of amine groups for use herein include, by wayof example, an amine of the general formula —R13N R14R15 wherein R13 isa C2-C30 alkylene, arylene, or cycloalkylene and R14 and R15 areindependently C1-C30 hydrocarbons such as, for example, alkyl groups,aryl groups, or cycloalkyl groups as defined herein, and the like.

Representative examples of an ureido group for use herein include, byway of example, an ureido group having one or more substituents orunsubstituted ureido. The ureido group preferably is an ureido grouphaving 1 to 12 carbon atoms. Examples of the substituents include alkylgroups and aryl groups. Examples of the ureido group include3-methylureido, 3,3-dimethylureido, and 3-phenylureido.

Representative examples of alkoxy groups for use herein include, by wayof example, an alkyl group as defined above attached via oxygen linkageto the rest of the molecule, i.e., of the general formula —OR20, whereinR20 is an alkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, aryl or anarylalkyl as defined above, e.g., —OCH3, —OC2H5, or —OC6H5, and thelike.

Representative examples of cycloalkyl groups for use herein include, byway of example, a substituted or unsubstituted non-aromatic mono ormulticyclic ring system of about 3 to about 18 carbon atoms such as, forexample, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,perhydronapththyl, adamantyl and norbornyl groups bridged cyclic groupor spirobicyclic groups, e.g., sprio-(4,4)-non-2-yl and the like,optionally containing one or more heteroatoms, e.g., O and N, and thelike.

Representative examples of cycloalkylalkyl groups for use hereininclude, by way of example, a substituted or unsubstituted cyclicring-containing radical containing from about 3 to about 18 carbon atomsdirectly attached to the alkyl group which are then attached to the mainstructure of the monomer at any carbon from the alkyl group that resultsin the creation of a stable structure such as, for example,cyclopropylmethyl, cyclobutylethyl, cyclopentylethyl and the like,wherein the cyclic ring can optionally contain one or more heteroatoms,e.g., O and N, and the like.

Representative examples of cycloalkenyl groups for use herein include,by way of example, a substituted or unsubstituted cyclic ring-containingradical containing from about 3 to about 18 carbon atoms with at leastone carbon-carbon double bond such as, for example, cyclopropenyl,cyclobutenyl, cyclopentenyl and the like, wherein the cyclic ring canoptionally contain one or more heteroatoms, e.g., O and N, and the like.

Representative examples of aryl groups for use herein include, by way ofexample, a substituted or unsubstituted monoaromatic or polyaromaticradical containing from about 5 to about 25 carbon atoms such as, forexample, phenyl, naphthyl, tetrahydronapthyl, indenyl, biphenyl and thelike, optionally containing one or more heteroatoms, e.g., O and N, andthe like.

Representative examples of arylalkyl groups for use herein include, byway of example, a substituted or unsubstituted aryl group as definedabove directly bonded to an alkyl group as defined above, e.g.,—CH2C6H5, —C2H5C6H5 and the like, wherein the aryl group can optionallycontain one or more heteroatoms, e.g., O and N, and the like.

Representative examples of fluoroaryl groups for use herein include, byway of example, an aryl group as defined above having one or morefluorine atoms attached to the aryl group.

Representative examples of heterocyclic ring groups for use hereininclude, by way of example, a substituted or unsubstituted stable 3 toabout 15 membered ring radical, containing carbon atoms and from one tofive heteroatoms, e.g., nitrogen, phosphorus, oxygen, sulfur andmixtures thereof. Suitable heterocyclic ring radicals for use herein maybe a monocyclic, bicyclic or tricyclic ring system, which may includefused, bridged or spiro ring systems, and the nitrogen, phosphorus,carbon, oxygen or sulfur atoms in the heterocyclic ring radical may beoptionally oxidized to various oxidation states. In addition, thenitrogen atom may be optionally quaternized; and the ring radical may bepartially or fully saturated (i.e., heteroaromatic or heteroarylaromatic). Examples of such heterocyclic ring radicals include, but arenot limited to, azetidinyl, acridinyl, benzodioxolyl, benzodioxanyl,benzofurnyl, carbazolyl, cinnolinyl, dioxolanyl, indolizinyl,naphthyridinyl, perhydroazepinyl, phenazinyl, phenothiazinyl,phenoxazinyl, phthalazinyl, pyridyl, pteridinyl, purinyl, quinazolinyl,quinoxalinyl, quinolinyl, isoquinolinyl, tetrazoyl, imidazolyl,tetrahydroisouinolyl, piperidinyl, piperazinyl, 2-oxopiperazinyl,2-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxoazepinyl, azepinyl, pyrrolyl,4-piperidonyl, pyrrolidinyl, pyrazinyl, pyrimidinyl, pyridazinyl,oxazolyl, oxazolinyl, oxasolidinyl, triazolyl, indanyl, isoxazolyl,isoxasolidinyl, morpholinyl, thiazolyl, thiazolinyl, thiazolidinyl,isothiazolyl, quinuclidinyl, isothiazolidinyl, indolyl, isoindolyl,indolinyl, isoindolinyl, octahydroindolyl, octahydroisoindolyl,quinolyl, isoquinolyl, decahydroisoquinolyl, benzimidazolyl,thiadiazolyl, benzopyranyl, benzothiazolyl, benzooxazolyl, furyl,tetrahydrofurtyl, tetrahydropyranyl, thienyl, benzothienyl,thiamorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone,dioxaphospholanyl, oxadiazolyl, chromanyl, isochromanyl and the like andmixtures thereof.

Representative examples of heteroaryl groups for use herein include, byway of example, a substituted or unsubstituted heterocyclic ring radicalas defined above. The heteroaryl ring radical may be attached to themain structure at any heteroatom or carbon atom that results in thecreation of a stable structure.

Representative examples of heteroarylalkyl groups for use hereininclude, by way of example, a substituted or unsubstituted heteroarylring radical as defined above directly bonded to an alkyl group asdefined above. The heteroarylalkyl radical may be attached to the mainstructure at any carbon atom from the alkyl group that results in thecreation of a stable structure.

Representative examples of heterocyclo groups for use herein include, byway of example, a substituted or unsubstituted heterocylic ring radicalas defined above. The heterocyclo ring radical may be attached to themain structure at any heteroatom or carbon atom that results in thecreation of a stable structure.

Representative examples of heterocycloalkyl groups for use hereininclude, by way of example, a substituted or unsubstituted heterocylicring radical as defined above directly bonded to an alkyl group asdefined above. The heterocycloalkyl radical may be attached to the mainstructure at carbon atom in the alkyl group that results in the creationof a stable structure.

Representative examples of a “polymerizable ethylenically unsaturatedorganic radicals” include, by way of example, (meth)acrylate-containingradicals, (meth)acrylamide-containing radicals,vinylcarbonate-containing radicals, vinylcarbamate-containing radicals,styrene-containing radicals and the like. In one embodiment, apolymerizable ethylenically unsaturated organic radical can berepresented by the general formula:

wherein R21 is hydrogen, fluorine or methyl; R22 is independentlyhydrogen, fluorine, or a —CO—Y—R24 radical wherein Y is —O—, —S— or —NH—and R24 is a divalent alkylene radical having 1 to about 10 carbonatoms.

The substituents in the ‘substituted alkyl’, ‘substituted alkoxy’,‘substituted cycloalkyl’, ‘substituted cycloalkylalkyl’, ‘substitutedcycloalkenyl’, ‘substituted arylalkyl’, ‘substituted aryl’, ‘substitutedheterocyclic ring’, ‘substituted heteroaryl ring,’ ‘substitutedheteroarylalkyl’, ‘substituted heterocycloalkyl ring’, ‘substitutedcyclic ring’ and ‘substituted carboxylic acid derivative’ may be thesame or different and include one or more substituents such as hydrogen,hydroxy, halogen, carboxyl, cyano, nitro, oxo (═O), thio(═S),substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy,substituted or unsubstituted alkenyl, substituted or unsubstitutedalkynyl, substituted or unsubstituted aryl, substituted or unsubstitutedarylalkyl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted cycloalkenyl, substituted or unsubstituted amino,substituted or unsubstituted aryl, substituted or unsubstitutedheteroaryl, substituted heterocycloalkyl ring, substituted orunsubstituted heteroarylalkyl, substituted or unsubstituted heterocyclicring, substituted or unsubstituted guanidine, —COORx, —C(O)Rx, —C(S)Rx,—C(O)NRxRy, —C(O)ONRxRy, —NRxCONRyRz, —N(Rx)SORy, —N(Rx)SO2Ry,—(═N—N(Rx)Ry), —NRxC(O)ORy, —NRxRy, —NRxC(O)Ry—, —NRxC(S)Ry—NRxC(S)NRyRz, —SONRxRy—, —SO2NRxRy-, —ORx, —ORxC(O)NRyRz, —ORxC(O)ORy—,—OC(O)Rx, —OC(O)NRxRy, —RxNRyC(O)Rz, —RxORy, —RxC(O)ORy, —RxC(O)NRyRz,—RxC(O)Rx, —RxOC(O)Ry, —SRx, —SORx, —SO2Rx, —ONO2, wherein Rx, Ry and Rzin each of the above groups can be the same or different and can be ahydrogen atom, substituted or unsubstituted alkyl, substituted orunsubstituted alkoxy, substituted or unsubstituted alkenyl, substitutedor unsubstituted alkynyl, substituted or unsubstituted aryl, substitutedor unsubstituted arylalkyl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted cycloalkenyl, substituted or unsubstitutedamino, substituted or unsubstituted aryl, substituted or unsubstitutedheteroaryl, ‘substituted heterocycloalkyl ring’ substituted orunsubstituted heteroarylalkyl, or a substituted or unsubstitutedheterocyclic ring.

Preferred monomers of Formula (I) are shown in Formulas (II)-(V) below:

A schematic representation of synthetic methods for making the novelcarboxylic silicon-containing monomers and polymers thereof as disclosedherein is provided below:

In a second aspect, the invention includes articles formed of deviceforming monomer mixes comprising the monomers of formula (I). Accordingto preferred embodiments, the article is the polymerization product of amixture comprising the aforementioned monomer and at least a secondmonomer. The invention is applicable to a wide variety of polymericmaterials, either rigid or soft. Especially preferred polymericmaterials are lenses including contact lenses, phakic and aphakicintraocular lenses and corneal implants although all polymeric materialsincluding biomaterials are contemplated as being within the scope ofthis invention. Preferred articles are optically clear and useful as acontact lens.

The present invention also provides medical devices such as heart valvesand films, surgical devices, vessel substitutes, intrauterine devices,membranes, diaphragms, surgical implants, blood vessels, artificialureters, artificial breast tissue and membranes intended to come intocontact with body fluid outside of the body, e.g., membranes for kidneydialysis and heart/lung machines and the like, catheters, mouth guards,denture liners, ophthalmic devices, and especially contact lenses.

Useful articles made with these materials may require hydrophobic,possibly silicon containing monomers. Preferred compositions have bothhydrophilic and hydrophobic monomers. Especially preferred issilicon-containing hydrogels.

Silicon-containing hydrogels are prepared by polymerizing a mixturecontaining at least one silicon-containing monomer and at least onehydrophilic monomer. The silicon-containing monomer may function as acrosslinking agent (a crosslinker being defined as a monomer havingmultiple polymerizable functionalities) or a separate crosslinker may beemployed.

An early example of a silicon-containing contact lens material isdisclosed in U.S. Pat. No. 4,153,641 (Deichert et al assigned to Bausch& Lomb Incorporated). Lenses are made from poly(organosiloxane) monomerswhich are α, ω terminally bonded through a divalent hydrocarbon group toa polymerized activated unsaturated group. Various hydrophobicsilicon-containing prepolymers such as1,3-bis(methacryloxyalkyl)polysiloxanes are copolymerized with knownhydrophilic monomers such as 2-hydroxyethyl methacrylate (HEMA).

U.S. Pat. No. 5,358,995 (Lai et al.) describes a silicon containinghydrogel which is comprised of an acrylic ester-capped polysiloxaneprepolymer, polymerized with a bulky polysiloxanylalkyl (meth)acrylatemonomer, and at least one hydrophilic monomer. Lai et al. is assigned toBausch & Lomb Incorporated and the entire disclosure is incorporatedherein by reference. The acrylic ester-capped polysiloxane prepolymer,commonly known as M₂D_(x) consists of two acrylic ester end groups and“x” number of repeating dimethylsiloxane units. The preferred bulkypolysiloxanylalkyl (meth)acrylate monomers are TRIS-type(methacryloxypropyltris(trimethylsiloxy)silane) with the hydrophilicmonomers being either acrylic- or vinyl-containing.

Other examples of silicon-containing monomer mixtures which may be usedwith this invention include the following: vinyl carbonate and vinylcarbamate monomer mixtures as disclosed in U.S. Pat. Nos. 5,070,215 and5,610,252 (Bambury et al); fluorosilicon monomer mixtures as disclosedin U.S. Pat. Nos. 5,321,108; 5,387,662 and 5,539,016 (Kunzler et al.);fumarate monomer mixtures as disclosed in U.S. Pat. Nos. 5,374,662;5,420,324 and 5,496,871 (Lai et al.) and urethane monomer mixtures asdisclosed in U.S. Pat. Nos. 5,451,651; 5,648,515; 5,639,908 and5,594,085 (Lai et al.), all of which are commonly assigned to assigneeherein Bausch & Lomb Incorporated, and the entire disclosures of whichare incorporated herein by reference.

Examples of non-silicon hydrophobic materials include alkyl acrylatesand methacrylates.

The carboxylic silicon-containing monomers may be copolymerized with awide variety of hydrophilic monomers to produce silicon hydrogel lenses.Suitable hydrophilic monomers include: unsaturated carboxylic acids,such as methacrylic and acrylic acids; acrylic substituted alcohols,such as 2-hydroxyethyl methacrylate and 2-hydroxyethyl acrylate; vinyllactams, such as N-vinylpyrrolidone (NVP) and 1-vinylazonan-2-one; andacrylamides, such as methacrylamide and N,N-dimethylacrylamide (DMA).

Still further examples are the hydrophilic vinyl carbonate or vinylcarbamate monomers disclosed in U.S. Pat. No. 5,070,215, and thehydrophilic oxazolone monomers disclosed in U.S. Pat. No. 4,910,277.Other suitable hydrophilic monomers will be apparent to one skilled inthe art.

Hydrophobic crosslinkers would include methacrylates such as ethyleneglycol dimethacrylate (EGDMA) and allyl methacrylate (AMA). In contrastto traditional silicon hydrogel monomer mixtures, the monomer mixturescontaining the carboxyl(ate) silicon-containing monomer of the inventionherein are relatively water soluble. This feature provides advantagesover traditional silicon hydrogel monomer mixtures in that there is lessrisk of incompatibility phase separation resulting in hazy lenses, thepolymerized materials are extractable with water. However, when desired,traditional organic extraction methods may also be used. Moreover,lenses prepared with the carboxyl(ate) silicon-containing monomers ofthe invention herein are wettable even without surface treatment,provide dry mold release, do not require solvents in the monomer mix(although solvents such as glycerol may be used), the extractedpolymerized material is not cytotoxic and the surface is lubricious tothe touch. In cases where the polymerized monomer mix containing thecarboxyl(ate) silicon-containing monomers of the invention herein do notdemonstrate a desirable tear strength, toughening agents such as TBE(4-t-butyl-2-hydroxycyclohexyl methacrylate) may be added to the monomermix. Other strengthening agents are well known to those of ordinaryskill in the art and may also be used when needed.

Although an advantage of the carboxylic silicon-containing monomersdisclosed herein is that they are relatively water soluble and alsosoluble in their comonomers, an organic diluent may be included in theinitial monomeric mixture. As used herein, the term “organic diluent”encompasses organic compounds which minimize incompatibility of thecomponents in the initial monomeric mixture and are substantiallynonreactive with the components in the initial mixture. Additionally,the organic diluent serves to minimize phase separation of polymerizedproducts produced by polymerization of the monomeric mixture. Also, theorganic diluent will generally be relatively non-inflammable.

Contemplated organic diluents include tert-butanol (TBA); diols, such asethylene glycol and polyols, such as glycerol. Preferably, the organicdiluent is sufficiently soluble in the extraction solvent to facilitateits removal from a cured article during the extraction step. Othersuitable organic diluents would be apparent to a person of ordinaryskill in the art.

The organic diluent is included in an amount effective to provide thedesired effect. Generally, the diluent is included at 5 to 60% by weightof the monomeric mixture, with 10 to 50% by weight being especiallypreferred.

According to the present process, the monomeric mixture, comprising atleast one hydrophilic monomer, at least one carboxylicsilicon-containing monomer and optionally the organic diluent, is shapedand cured by conventional methods such as static casting or spincasting.

Lens formation can be by free radical polymerization such asazobisisobutyronitrile (AIBN) and peroxide catalysts using initiatorsand under conditions such as those set forth in U.S. Pat. No. 3,808,179,incorporated herein by reference. Photoinitiation of polymerization ofthe monomer mixture as is well known in the art may also be used in theprocess of forming an article as disclosed herein. Colorants and thelike may be added prior to monomer polymerization.

Subsequently, a sufficient amount of unreacted monomer and, whenpresent, organic diluent is removed from the cured article to improvethe biocompatibility of the article. Release of non-polymerized monomersinto the eye upon installation of a lens can cause irritation and otherproblems. Unlike other monomer mixtures that must be extracted withflammable solvents such as isopropyl alcohol, because of the propertiesof the novel carboxyl(ate) siloxane monomers disclosed herein,non-flammable solvents including water may be used for the extractionprocess.

Once the biomaterials formed from the polymerized monomer mix containingthe carboxylic silicon containing monomers disclosed herein are formedthey are then extracted to prepare them for packaging and eventual use.Extraction is accomplished by exposing the polymerized materials tovarious solvents such as water, tert-butanol, etc. for varying periodsof time. For example, one extraction process is to immerse thepolymerized materials in water for about three minutes, remove the waterand then immerse the polymerized materials in another aliquot of waterfor about three minutes, remove that aliquot of water and then autoclavethe polymerized material in water or buffer solution.

Following extraction of unreacted monomers and any organic diluent, theshaped article, for example an RGP lens, is optionally machined byvarious processes known in the art. The machining step includes lathecutting a lens surface, lathe cutting a lens edge, buffing a lens edgeor polishing a lens edge or surface. The present process is particularlyadvantageous for processes wherein a lens surface is lathe cut, sincemachining of a lens surface is especially difficult when the surface istacky or rubbery.

Generally, such machining processes are performed before the article isreleased from a mold part. After the machining operation, the lens canbe released from the mold part and hydrated. Alternately, the articlecan be machined after removal from the mold part and then hydrated.

EXAMPLES

All solvents and reagents are obtained from Sigma-Aldrich, Milwaukee,Wis., and used as is. The monomers 2-hydroxyethyl methacrylate and1-vinyl-2-pyrrolidone are purified using standard techniques.

Analytical Measurements

ESI-TOF MS: The electrospray (ESI) time of flight (TOF) MS analysis isperformed on an Applied Biosystems Mariner instrument. The instrumentoperated in positive ion mode. The instrument is mass calibrated with astandard solution containing lysine, angiotensinogen, bradykinin(fragment 1-5) and des-Pro bradykinin. This mixture provides aseven-point calibration from 147 to 921 m/z. The applied voltageparameters are optimized from signal obtained from the same standardsolution. For exact mass measurements poly(ethylene glycol) (PEG),having a nominal M_(n) value of 400 Da, is added to the sample ofinterest and used as an internal mass standard. Two PEG oligomers thatbracketed the sample mass of interest are used to calibrate the massscale. Samples are prepared as 30 μM solutions in isopropanol (IPA) withthe addition of 2% by volume saturated NaCl in IPA. Samples are directlyinfused into the ESI-TOF MS instrument at a rate of 35 μL/min. Asufficient resolving power (6000 RP m/Δm FWHM) is achieved in theanalysis to obtain the monoistopic mass for each sample. In eachanalysis the experimental monoisotopic mass is compared to thetheoretical monoisotopic mass as determined from the respectiveelemental compositions. In each analysis the monoisotopic masscomparison is less than 10 ppm error. It should be noted that unchargedsamples have a sodium (Na) atom included in their elemental composition.This Na atom occurs as a necessary charge agent added in the samplepreparation procedure. Some samples do not require an added charge agentsince they contain a charge from the quaternary nitrogen inherent totheir respective structure.

GC: Gas chromatography is performed using a Hewlett Packard HP 6890Series GC System. Purities are determined by integration of the primarypeak and comparison to the normalized chromatograph.

NMR: ¹H-NMR characterization is carried out using a 400 MHz Varianspectrometer using standard techniques in the art. Samples are dissolvedin chloroform-d (99.8 atom % D), unless otherwise noted. Chemical shiftsare determined by assigning the residual chloroform peak at 7.25 ppm.Peak areas and proton ratios are determined by integration of baselineseparated peaks. Splitting patterns (s=singlet, d=doublet, t=triplet,q=quartet, m=multiplet, br=broad) and coupling constants (J/Hz) arereported when present and clearly distinguishable.

Mechanical properties and Oxygen Permeability: Modulus and elongationtests are conducted according to ASTM D-1708a, employing an Instron(Model 4502) instrument where the hydrogel film sample is immersed inborate buffered saline; an appropriate size of the film sample is gaugelength 22 mm and width 4.75 mm, where the sample further has endsforming a dog bone shape to accommodate gripping of the sample withclamps of the Instron instrument, and a thickness of 200+50 microns.

Oxygen permeability (also referred to as Dk) is determined by thefollowing procedure. Other methods and/or instruments may be used aslong as the oxygen permeability values obtained therefrom are equivalentto the described method. The oxygen permeability of silicon-containinghydrogels is measured by the polarographic method (ANSI Z80.20-1998)using an O2 Permeometer Model 201T instrument (Createch, Albany, Calif.USA) having a probe containing a central, circular gold cathode at itsend and a silver anode insulated from the cathode. Measurements aretaken only on pre-inspected pinhole-free, flat silicon-containinghydrogel film samples of three different center thicknesses ranging from150 to 600 microns. Center thickness measurements of the film samplesmay be measured using a Rehder ET-1 electronic thickness gauge.Generally, the film samples have the shape of a circular disk.Measurements are taken with the film sample and probe immersed in a bathcontaining circulating phosphate buffered saline (PBS) equilibrated at35° C.+/−0.2°. Prior to immersing the probe and film sample in the PBSbath, the film sample is placed and centered on the cathode premoistenedwith the equilibrated PBS, ensuring no air bubbles or excess PBS existsbetween the cathode and the film sample, and the film sample is thensecured to the probe with a mounting cap, with the cathode portion ofthe probe contacting only the film sample. For silicon-containinghydrogel films, it is frequently useful to employ a Teflon polymermembrane, e.g., having a circular disk shape, between the probe cathodeand the film sample. In such cases, the Teflon membrane is first placedon the pre-moistened cathode, and then the film sample is placed on theTeflon membrane, ensuring no air bubbles or excess PBS exists beneaththe Teflon membrane or film sample. Once measurements are collected,only data with correlation coefficient value (R2) of 0.97 or highershould be entered into the calculation of Dk value. At least two Dkmeasurements per thickness, and meeting R2 value, are obtained. Usingknown regression analyses, oxygen permeability (Dk) is calculated fromthe film samples having at least three different thicknesses. Any filmsamples hydrated with solutions other than PBS are first soaked inpurified water and allowed to equilibrate for at least 24 hours, andthen soaked in PHB and allowed to equilibrate for at least 12 hours. Theinstruments are regularly cleaned and regularly calibrated using RGPstandards. Upper and lower limits are established by calculating a+/−8.8% of the Repository values established by William J. Benjamin, etal., The Oxygen Permeability of Reference Materials, Optom Vis Sci 7(12s): 95 (1997), the disclosure of which is incorporated herein in itsentirety:

Material Name Repository Values Lower Limit Upper Limit Fluoroperm 3026.2 24 29 Menicon EX 62.4 56 66 Quantum II 92.9 85 101Abbreviations

-   NVP 1-Vinyl-2-pyrrolidone-   TRIS Methacryloxypropyltris(trimethylsiloxy)silane-   HEMA 2-Hydroxyethyl methacrylate-   v-64 2,2′-Azobis(2-methylpropionitrile)-   PG 1,3-Propanediol-   EGDMA Ethylene glycol dimethacrylate-   SA 2-[3-(2H-Benzotriazol-2-yl)-4-hydroxyphenyl]ethyl methacrylate-   IMVT 1,4-bis[4-(2-methacryloxyethyl)phenylamino]anthraquinone    Unless otherwise specifically stated or made clear by its usage, all    numbers used in the examples should be considered to be modified by    the term “about” and to be weight percent.

EXAMPLE 1 Synthesis of Carboxylic Siloxanyl Monomer

This method is adapted from a literature procedure: Zilkha, A and Golik,U. J. Org. Chem. 1963, 28, 2007-2009. To a stirred solution of itaconicanhydride (4.24 g, 37.8 mmol) in CHCl₃ (40 mL) is slowly added3-aminopropyltris(trimethylsiloxy)silane (15.1 mL, 38.0 mmol) at 0° C.under a nitrogen atmosphere. The cooling bath is removed and thesolution allowed to warm to ambient temperature and stirred under anitrogen atmosphere an additional 15 h. Following removal of solvent atreduced pressure, the viscous, clear oil is analyzed via massspectrometry to confirm the presence of the proposed structure.

EXAMPLE 2 Polymerization, Processing and Properties of Films ContainingCarboxylic Siloxanyl Monomers

Liquid monomer solutions containing carboxylic siloxanyl monomers fromexample 1 above, along with other additives common to ophthalmicmaterials (diluent, initiator, etc.) are clamped between silanized glassplates at various thicknesses and polymerized using thermaldecomposition of the free-radical generating additive by heating 2 h at100° C. under a nitrogen atmosphere.

EXAMPLE 3 Synthesis of Carboxylate Siloxanyl Monomer

Using methods well known in the art, the product from example 1 can beconverted by treatment with base and optionally ion-exchange to affordcarboxylate derivatives as shown below.

EXAMPLES 4-11 Polymerization and Processing of Films Containing ofPrepolymers.

Liquid monomer solutions containing carboxylate siloxanyl monomer fromexample 3 above, along with other monomers and additives common toophthalmic materials (diluent, initiator, etc.) can be clamped betweensilanized glass plates at various thicknesses and polymerized usingthermal decomposition of the free radical generating additive by heating2 h at 100° C. under a nitrogen atmosphere.

Contemplated formulations are listed in table 1.

TABLE 1 Ex- Ex- am- am- ple ple 3 NVP HEMA TRIS HFIPMA PG EGDMA ν-64 410.0 0.0 10.0 50.0 25.0 4.0 0.5 0.5 5 10.0 20.0 0.0 45.0 20.0 4.0 0.50.5 6 25.0 25.0 10.0 0.0 35.0 4.0 0.5 0.5 7 10.0 50.0 10.0 25.0 0.0 4.00.5 0.5 8 10.0 25.0 10.0 25.0 25.0 0.0 0.5 0.5 9 10.0 25.0 10.0 25.525.0 4.0 0.0 0.5 10 35.0 50.0 10.0 0.0 0.0 4.0 0.5 0.5 11 45.0 50.5 0.00.0 0.0 4.0 0.0 0.5

EXAMPLE 12

Films are removed from glass plates and hydrated/extracted in deionizedH₂O for a minimum of 4 h, transferred to fresh deionized H₂O andautoclaved 30 min at 121° C. The cooled films are then analyzed forselected properties of interest in ophthalmic materials as described.Mechanical tests are conducted in borate buffered saline according toASTM D-1708a, discussed above. The oxygen permeabilities, reported in Dk(or barrer) units, are measured in phosphate buffered saline at 35° C.,using acceptable films with three different thicknesses, as discussedabove.

EXAMPLE 13 Polymerization and Processing of Ophthalmic Lenses ContainingCarboxylate Siloxanyl Monomer

40 uL aliquots of a soluble, liquid monomer mix containing 13.9 parts byweight of the product from example 3, 23.3 parts TRIS, 41.8 parts NVP,13.9 parts HEMA, 5 parts PG, 0.5 parts v-64, 1.5 parts SA, and 60 ppmIMVT are sealed between poly(propylene) anterior and posterior contactlens molds under an inert nitrogen atmosphere, transferred to an ovenand heated under an inert nitrogen atmosphere 2 h at 100° C. The cooledmold pairs are separated and the dry lens released from the mold,hydrated/extracted twice in deionized H2O for a minimum of 3 min,transferred to and sealed in an autoclave vial containing a bufferedsaline solution and autoclaved 30 min at 121° C.

1. A monomer of formula (I):

wherein L can be the same or different and is selected from the divalentgroup consisting of a bond, a straight or branched C1-C30 alkyl group, aC1-C30 fluoroalkyl group, a C1-C20 ester-containing group, an alkylether, cycloalkyl ether cycloalkenyl ether, aryl ether, arylalkyl ether,a polyether containing group, amide group, amine group, a substituted orunsubstituted C3-C30 cycloalkyl group, a substituted or unsubstitutedC3-C30 cycloalkylalkyl group, a substituted or unsubstituted C3-C30cycloalkenyl group, a substituted or unsubstituted C5-C30 aryl group, asubstituted or unsubstituted C5-C30 arylalkyl group, a substituted orunsubstituted C5-C30 heteroaryl group, a substituted or unsubstitutedC3-C30 heterocyclic ring, a substituted or unsubstituted C4-C30heterocyclolalkyl group, a substituted or unsubstituted C6-C30heteroarylalkyl group, a C5-C30 fluoroaryl group, a hydroxyl substitutedalkyl ether and combinations thereof; X is H, one equivalent alkalimetal, or ½ equivalent alkaline earth metal; R is a trimethylsiloxanylgroup and V is independently a polymerizable ethylenically unsaturatedorganic radical.
 2. The monomer of claim 1 having a formula selectedfrom the following formulae:


3. A monomer mix useful for making polymerized biomaterials comprisingat least one monomer of claim 1 and at least one second monomer.
 4. Themonomer mix of claim 3, further comprising in addition to the secondmonomer a hydrophobic monomer and a hydrophilic monomer.
 5. The monomermix of claim 3 wherein the second monomer is selected from the groupconsisting of unsaturated carboxylic acids, itaconic acid esters,acrylic substituted alcohols, vinyl lactams, acrylamides, methacrylates,hydrophilic vinyl carbonates, hydrophilic vinyl carbamate monomers,hydrophilic oxazolone monomers, and mixtures thereof.
 6. The monomer mixof claim 3, wherein the second monomer is selected from the groupconsisting of methacrylic acid, acrylic acid, itaconic acid,2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate,N-vinylpyrrolidone, N-vinylcaprolactone, methacrylamide,N,N-dimethylacrylamide, ethylene glycol dimethacrylate, methylmethacrylate, allyl methacrylate, 3-methacryloxypropyltris(trimethylsiloxy)silane and mixtures thereof.
 7. A biomedical devicecomprising a polymerization product of the monomer mix of claim
 3. 8.The biomedical device of claim 7, wherein the device is a contact lens.9. The biomedical device of claim 8, wherein the contact lens is a rigidgas permeable contact lens, a soft contact lens or a hydrogel contactlens.
 10. The biomedical device of claim 7, wherein the device is anintraocular lens.
 11. The biomedical device of claim 10, wherein theintraocular lens is a phakic intraocular lens or an aphakic intraocularlens.
 12. The biomedical device of claim 7, wherein the device is acorneal implant.
 13. A biomedical device comprising a polymerizationproduct of a monomer mixture comprising at least one monomer of claim 1and at least one second monomer.
 14. The biomedical device of claim 13,wherein the second monomer is selected from the group consisting ofmethacrylic acid, acrylic acid, itaconic acid, 2-hydroxyethylmethacrylate, 2-hydroxyethyl acrylate, N-vinylpyrrolidone,N-vinylcaprolactone, methacrylamide, N,N-dimethylacrylamide, ethyleneglycol dimethacrylate, methyl methacrylate, allyl methacrylate, 3-methacryloxypropyl tris(trimethylsiloxy)silane and mixtures thereof.15. The biomedical device of claim 13, wherein the device is selectedfrom the group consisting of heart valves, intraocular lenses, films,surgical devices, vessel substitutes, intrauterine devices, membranes,diaphragms, surgical implants, blood vessels, artificial ureters,artificial breast tissue, membranes for kidney dialysis machines,membranes for heart/lung machines, catheters, mouth guards, dentureliners, ophthalmic devices, and contact lenses.
 16. The biomedicaldevice of claim 13, wherein the device is a contact lens.
 17. A methodof making a biomedical device comprising: providing a monomer mixturecomprising the monomer of claim 1 and at least a second monomer;subjecting the monomer mixture to polymerizing conditions to provide apolymerized device; and extracting the unpolymerized monomers from thepolymerized device.
 18. The method of claim 17 wherein the step ofextracting is performed with non-flammable solvents.
 19. The method ofclaim 17 wherein the step of extracting is performed with water.
 20. Themethod of claim 17, further comprising the step of packaging andsterilizing the polymerized device.